January 31, 2014

Biologists make first mouse model for MERS

A remedy for Middle East respiratory syndrome (MERS), the coronavirus outbreak from Saudi Arabia that has killed 77 of the 180 people who have contracted it, has so far eluded researchers. But they have now created the first mouse model of the disease, which could enable faster testing of drugs and vaccines. The method used to make mice susceptible to MERS might also provide a quick way to study future pandemic viruses in mice.

The coronavirus infects humans by binding to a protein, called DPP4, that sits on the surface of cells in the lungs. But the structure of the mouse version of DPP4 is different and the virus does not bind to it. The virus does infect macaques and marmosets, which develop a mild form of the disease, and researchers have begun using them to test vaccines and drugs. Yet working with monkeys is expensive and slow.

To create a more practical model, Stanley Perlman, a microbiologist of the University of Iowa in Iowa City, and his colleagues put the gene encoding human DPP4 into an adenovirus to which mice are susceptible.

They exposed the mice to the adenovirus — similar to a cold virus — through inhaled droplets that entered their lungs. Once the adenovirus had invaded cells in the lungs, the cells began making the human DPP4 protein and expressing it on their surfaces.

When the researchers then had the mice inhale droplets containing the MERS coronavirus, the coronavirus bound to the human receptor and began taking over the cells. “The animals are walking around as bags of viruses,” said Perlman, in a 29 January presentation at a meeting of the American Society for Microbiology in Washington DC.

The animals’ immune systems responded and made antibodies to attack the MERS virus. The mice never became sick or lost weight, however, which is something of a mystery, says Perlman, although he points out that it is not unusual for human viral diseases to have milder effects in mice.

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A remedy for Middle East respiratory syndrome (MERS), the coronavirus outbreak from Saudi Arabia that has killed 77 of the 180 people who have contracted it, has so far eluded researchers. But they have now created the first mouse model of the disease, which could enable faster testing of drugs and vaccines. The method used to make mice susceptible to MERS might also provide a quick way to study future pandemic viruses in mice.

The coronavirus infects humans by binding to a protein, called DPP4, that sits on the surface of cells in the lungs. But the structure of the mouse version of DPP4 is different and the virus does not bind to it. The virus does infect macaques and marmosets, which develop a mild form of the disease, and researchers have begun using them to test vaccines and drugs. Yet working with monkeys is expensive and slow.

To create a more practical model, Stanley Perlman, a microbiologist of the University of Iowa in Iowa City, and his colleagues put the gene encoding human DPP4 into an adenovirus to which mice are susceptible.

They exposed the mice to the adenovirus — similar to a cold virus — through inhaled droplets that entered their lungs. Once the adenovirus had invaded cells in the lungs, the cells began making the human DPP4 protein and expressing it on their surfaces.

When the researchers then had the mice inhale droplets containing the MERS coronavirus, the coronavirus bound to the human receptor and began taking over the cells. “The animals are walking around as bags of viruses,” said Perlman, in a 29 January presentation at a meeting of the American Society for Microbiology in Washington DC.

The animals’ immune systems responded and made antibodies to attack the MERS virus. The mice never became sick or lost weight, however, which is something of a mystery, says Perlman, although he points out that it is not unusual for human viral diseases to have milder effects in mice.